Chronic exposure to trichothecenes is known to disturb insulin-like growth factor 1 and signaling of insulin and leptin hormones and causes considerable growth retardation in animals. However, limited information was available on mechanisms underlying trichothecene-induced growth retardation. In this study, we employed an integrated transcriptomics, proteomics, and RNA interference (RNAi) approach to study the molecular mechanisms underlying trichothecene cytotoxicity in rat pituitary adenoma GH3 cells. Our results showed that trichothecenes suppressed the synthesis of growth hormone 1 (Gh1) and inhibited the eukaryotic transcription and translation initiation by suppressing aminoacyl-tRNA synthetases transcription, inducing eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2) and reducing eukaryotic translation initiation factor 5 a. The sulfhydryl oxidases , protein disulfide isomerase,and heat shock protein 90 (were greatly reduced, which resulted in adverse regulation of protein processing and folding. Differential genes and proteins associated with a decline in energy metabolism and cell cycle arrest were also found in our study. However, use of RNAi to interfere with hemopoietic cell kinase (Hck) and EIF2AK2 transcriptions or use of chemical inhibitors of MAPK, p38, Ras, and JNK partially reversed the reduction of Gh1 levels induced by trichothecenes. It indicated that the activation of MAPKs, Hck, and EIF2AK2 were important for trichothecene-induced growth hormone suppression. Considering the potential hazards of exposure to trichothecenes, our findings could help to improve our understanding regarding human and animal health implications.

*National Reference Laboratory of Veterinary Drug Residues and MAO Key Laboratory for Detection of Veterinary Drug Residues; College of Life Science Yangtze University Jingzhou Hubei China; and Center for Basic and Applied Research Faculty of Informatics and Management University of Hradec Kralove Hradec Kralove Czech Republic

*National Reference Laboratory of Veterinary Drug Residues and MAO Key Laboratory for Detection of Veterinary Drug Residues; Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety Wuhan Hubei China;

*National Reference Laboratory of Veterinary Drug Residues and MAO Key Laboratory for Detection of Veterinary Drug Residues; MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products Huazhong Agricultural University;

*National Reference Laboratory of Veterinary Drug Residues and MAO Key Laboratory for Detection of Veterinary Drug Residues; MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products Huazhong Agricultural University; Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety Wuhan Hubei China;

*National Reference Laboratory of Veterinary Drug Residues and MAO Key Laboratory for Detection of Veterinary Drug Residues; MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products Huazhong Agricultural University; Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety Wuhan Hubei China; Research Center of Healthy Livestock Institute of Subtropical Agriculture Chinese Academy of Sciences Changsha China;

MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products Huazhong Agricultural University; Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety Wuhan Hubei China;

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